CN117736104A - Method for synthesizing butanedicarboxylate derivative by visible light catalysis - Google Patents
Method for synthesizing butanedicarboxylate derivative by visible light catalysis Download PDFInfo
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- CN117736104A CN117736104A CN202311590564.0A CN202311590564A CN117736104A CN 117736104 A CN117736104 A CN 117736104A CN 202311590564 A CN202311590564 A CN 202311590564A CN 117736104 A CN117736104 A CN 117736104A
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- 238000000034 method Methods 0.000 title claims abstract description 30
- VQDJODAWOFNASI-UHFFFAOYSA-N 2-propylpropanedioic acid Chemical class CCCC(C(O)=O)C(O)=O VQDJODAWOFNASI-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 13
- 238000006555 catalytic reaction Methods 0.000 title claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- -1 butanedioic acid ester Chemical class 0.000 claims abstract description 33
- 239000002994 raw material Substances 0.000 claims abstract description 14
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 claims abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 75
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 239000000470 constituent Substances 0.000 claims description 2
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 abstract description 5
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 abstract description 4
- 239000012847 fine chemical Substances 0.000 abstract description 3
- 238000002360 preparation method Methods 0.000 abstract description 3
- 238000006462 rearrangement reaction Methods 0.000 abstract description 3
- 229960005137 succinic acid Drugs 0.000 abstract description 3
- 125000003107 substituted aryl group Chemical group 0.000 abstract description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 abstract 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 abstract 1
- 239000000047 product Substances 0.000 description 45
- 230000015572 biosynthetic process Effects 0.000 description 38
- 238000003786 synthesis reaction Methods 0.000 description 38
- CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical compound COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 37
- 238000004440 column chromatography Methods 0.000 description 23
- 239000003480 eluent Substances 0.000 description 21
- 239000007788 liquid Substances 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 13
- LEWVLNKSZUIEKO-UHFFFAOYSA-N methyl 2-(n-methylanilino)acetate Chemical compound COC(=O)CN(C)C1=CC=CC=C1 LEWVLNKSZUIEKO-UHFFFAOYSA-N 0.000 description 13
- 239000007858 starting material Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000000746 purification Methods 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 5
- 239000012954 diazonium Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000006981 Stevens rearrangement reaction Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 3
- ZQYLDVNTWDEAJI-UHFFFAOYSA-N methyl 2-(4-methoxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(OC)C=C1 ZQYLDVNTWDEAJI-UHFFFAOYSA-N 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 238000007036 catalytic synthesis reaction Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- GMEBDKGPPKAPEM-UHFFFAOYSA-N methyl 2-[3-(trifluoromethyl)phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(C(F)(F)F)=C1 GMEBDKGPPKAPEM-UHFFFAOYSA-N 0.000 description 2
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 150000003900 succinic acid esters Chemical class 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- SKYXLDSRLNRAPS-UHFFFAOYSA-N 1,2,4-trifluoro-5-methoxybenzene Chemical compound COC1=CC(F)=C(F)C=C1F SKYXLDSRLNRAPS-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- ISZSNDRUUXEBHR-UHFFFAOYSA-N 2-(n,3-dimethylanilino)propanoic acid Chemical compound OC(=O)C(C)N(C)C1=CC=CC(C)=C1 ISZSNDRUUXEBHR-UHFFFAOYSA-N 0.000 description 1
- JDTUPLBMGDDPJS-UHFFFAOYSA-N 2-methoxy-2-phenylethanol Chemical compound COC(CO)C1=CC=CC=C1 JDTUPLBMGDDPJS-UHFFFAOYSA-N 0.000 description 1
- 125000006279 3-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Br)=C1[H])C([H])([H])* 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- PZVWKCGKIADPAU-UHFFFAOYSA-N 4-(1,3-benzothiazol-2-ylsulfanyl)aniline Chemical compound C1=CC(N)=CC=C1SC1=NC2=CC=CC=C2S1 PZVWKCGKIADPAU-UHFFFAOYSA-N 0.000 description 1
- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- QDZARNQKIZUXDK-UHFFFAOYSA-N [C-][N+]#N Chemical class [C-][N+]#N QDZARNQKIZUXDK-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- GRKUXCWELVWVMZ-UHFFFAOYSA-N amino acetate Chemical class CC(=O)ON GRKUXCWELVWVMZ-UHFFFAOYSA-N 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940089960 chloroacetate Drugs 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- ULSSGHADTSRELG-UHFFFAOYSA-N methyl 2-(3-bromophenyl)acetate Chemical compound COC(=O)CC1=CC=CC(Br)=C1 ULSSGHADTSRELG-UHFFFAOYSA-N 0.000 description 1
- QHJOWSXZDCTNQX-UHFFFAOYSA-N methyl 2-(4-bromophenyl)acetate Chemical compound COC(=O)CC1=CC=C(Br)C=C1 QHJOWSXZDCTNQX-UHFFFAOYSA-N 0.000 description 1
- OHTZXQYRHDVXLJ-UHFFFAOYSA-N methyl 2-(4-cyanophenyl)acetate Chemical compound COC(=O)CC1=CC=C(C#N)C=C1 OHTZXQYRHDVXLJ-UHFFFAOYSA-N 0.000 description 1
- AJPPKGMEHMXPMC-UHFFFAOYSA-N methyl 2-(4-fluorophenyl)acetate Chemical compound COC(=O)CC1=CC=C(F)C=C1 AJPPKGMEHMXPMC-UHFFFAOYSA-N 0.000 description 1
- OUWFDISHMBDYON-UHFFFAOYSA-N methyl 2-(4-phenylmethoxyphenyl)acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OCC1=CC=CC=C1 OUWFDISHMBDYON-UHFFFAOYSA-N 0.000 description 1
- MYXWDGHDOAZQJT-UHFFFAOYSA-N methyl 2-(n,4-dimethylanilino)acetate Chemical compound COC(=O)CN(C)C1=CC=C(C)C=C1 MYXWDGHDOAZQJT-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- AEHDSYHVTDJGDN-UHFFFAOYSA-M phenacyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1C(=O)C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 AEHDSYHVTDJGDN-UHFFFAOYSA-M 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing a butanedicarboxylate derivative by visible light catalysis, belonging to the technical fields of chemical pharmacy and fine chemical preparation. The invention takes various substituted aryl diazo acetate and amino acetate as raw materials, and the required butanedicarboxylate derivative is obtained by the rearrangement reaction under the irradiation of blue light. The reaction condition is mild, and the operation is simple. The invention provides a simple and practical technical route for preparing the butanedioic acid ester derivative, and has wide application in the technical fields of chemical pharmacy and fine chemical preparation.
Description
Technical Field
The invention belongs to the technical field of chemical pharmacy and fine chemical preparation, and particularly relates to a method for synthesizing a butanecarboxylate derivative by using visible light catalysis, which mainly relates to a diazonium carbene rearrangement reaction by using visible light catalysis.
Background
Butanedicarboxylic acid derivatives are a very important structural framework in organic chemistry and pharmaceutical chemistry. The butanedioic acid ester is also called succinic acid ester, has wide application in the industrial field, is an important chemical intermediate, and can be used for synthesizing important chemical products such as succinic anhydride, succinimide and the like, and the formula is shown as follows:
the synthesis method of the 2, 3-disubstituted succinate is more, and common methods include esterification of succinic acid, alcoholysis of succinyl chloride and the like. Diazo compounds are common carbene precursors, and can generate carbene active intermediates through photoinduction, metal catalysis, acid catalysis, biocatalysis and the like, wherein transition metal catalysis is mature. For example, patent CN105294471a uses diazonium, aromatic amine, nitroolefin ester as raw material, rhodium complex as catalyst, chiral diene ligand as catalyst, organic solvent as solvent, molecular sieve as water absorbent, after one-step reaction, the solvent is removed to obtain crude product, and column chromatography is performed to obtain alpha-amino-gamma-nitrosuccinate derivative with high enantioselectivity.
The chemical reaction catalyzed by the visible light has the advantages of environmental protection, simple operation, mild condition and the like, and is a hot spot for research in recent years. In 2019, the Koenigs group reported a visible light mediated [2,3] -Sigmatropic rearrangement of amines and diazocarbenes (Synthesis 2019,51,4348), as shown in the following formula:
however, stevens rearrangement by visible light mediated amine compounds and diazocarbenes has not been reported.
Disclosure of Invention
The invention aims to provide a method for synthesizing a butanedicarboxylate derivative by using visible light as a catalyst, which takes various substituted aryl diazo acetates and amino acetates as raw materials, and performs rearrangement reaction under blue light irradiation to obtain the required butanedicarboxylate derivative. The reaction has high yield, mild condition and simple operation.
The butanedicarboxylate derivative provided by the invention is shown as a formula (1), wherein the 2 and 3 positions of the butanedicarboxylate derivative are provided with substituent groups, and the butanedicarboxylate derivative is obtained by carrying out Stevens rearrangement reaction on substituted aryl diazoacetate and amino acetate serving as raw materials under blue light irradiation. Such reactions are traditionally carried out by transition metal catalysis.
Wherein R is 1 、R 2 Each independently is any one of alkyl, alkoxy, aryl; or R is 1 、R 2 Is a constituent part of the same annular structure; r is R 3 、R 4 And R is 5 Each independently is any one of alkyl, aryl, allyl.
The specific synthetic route of the visible light catalytic synthesis of the butyldicarboxylate derivative provided by the invention is as follows:
wherein R is 1 Is any one of alkyl, alkoxy and aryl;
R 2 is any one of alkyl, alkoxy and aryl;
R 1 and R is 2 But may also be part of the same ring structure.
R 3 、R 4 And R is 5 Respectively any of alkyl, aryl and allylOne of the two.
Preferably, R 1 、R 2 Is any one of alkyl and aryl; r is R 4 Is an alkyl group; r is R 3 Is phenyl or substituted aryl; r is R 5 Is an alkyl group.
The specific operation steps of the visible light catalytic synthesis of the butanedicarboxylate derivative provided by the invention are as follows:
at room temperature, the amino acetate and the substituted aryl diazoacetate serving as reaction raw materials are dissolved in an organic solvent, then the reaction system is placed in a nitrogen atmosphere, and after the reaction system is stirred for a certain time at room temperature under the irradiation of blue LED light, the required butanedioic acid ester derivative is obtained through column chromatography and chromatographic separation.
The concentration of the reaction raw material in the reaction system used is 0.05 to 0.8mol/L, preferably 0.4mol/L.
The equivalent ratio of the amino acetate to the substituted aryl diazoacetate used as the reaction raw material is 2-30:6, preferably 2:6.
The organic solvent used is dichloromethane, 1, 2-dichloroethane, chloroform, etc., preferably dichloromethane.
The blue LED lamp used is a blue light with a wavelength of 450 to 500 nm, preferably 470 nm.
The light reaction time was 12 hours.
The invention provides a method for synthesizing a butanedicarboxylate derivative, wherein a possible reaction mechanism is shown in a figure 1, and the butanedicarboxylate derivative is obtained through visible light-mediated Stevens rearrangement of amine compounds and diazocarbene. The synthesis method does not need any catalyst or additive, can react only by using blue light in visible light for irradiation, has low cost, is green and environment-friendly, has mild reaction conditions, is very simple and convenient to operate, and is favorable for subsequent industrialized large-scale synthesis. The invention provides a practical technical route for synthesizing related butanedicarboxylate derivatives.
Drawings
FIG. 1 is a diagram of the reaction mechanism of the present invention.
Detailed Description
The invention is further illustrated by the following examples.
The following non-limiting examples are intended to illustrate the invention, but not to limit it, and any modifications and variations within the spirit of the invention and the scope of the claims are within the scope of the invention.
The reagents, catalysts and solvents used in the invention are all commercially purchased or synthesized according to literature reports, and the solvents are refined and purified before use.
Example 1
Synthesis of methyl phenylacetate diazonium: methyl phenylacetate (1.4 mL,10 mmol) and acetaminophenesulfonyl azide (2.88 g,12 mmol) were dissolved in 15mL acetonitrile in a 100mL reaction flask. 1, 8-diazabicyclo [5.4.0] undec-7-ene (2.1 mL,14 mmol) was slowly added dropwise under ice-bath and stirred for 10 minutes. The ice bath was removed and the mixture was stirred at ambient temperature for 4h, after which acetonitrile was removed under reduced pressure. The mixture was extracted three times with an appropriate amount of ethyl acetate and water, the organic phase was dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (eluent V (PE): V (EA) =50:1) to give the product methyl phenylacetate diazonium in 90% yield.
Synthesis of dimethyl 2- (methyl (phenyl) amino) -3-phenylsuccinate (3 a/3 a'): 35.2mg (0.2 mmol,1 eq) of methyl phenylacetate diazo and 107.5mg (0.6 mmol,3 eq) of methyl N-methyl-N-phenyl-glycinate are added to dichloromethane (2 mL) at room temperature, in N 2 The reaction was irradiated for 12h under 470nm blue light. The product 3a and 3a', which are diastereoisomers with a total yield of 76%, was obtained by column chromatography separation and purification (eluent V (PE): V (1, 4-dioxane) =50:1). Wherein 3a (29.4 mg), a white solid, 3a' (20.5 mg) was a colorless liquid. 3a: 1 H NMR(400MHz,CDCl 3 ):δ7.49-7.47(m,2H),7.33-7.24(m,5H),7.03(d,J＝8.9Hz,2H),6.82(t,J＝7.5Hz,1H),5.11(d,J＝11.6Hz,1H),4.41(d,J＝11.7Hz,1H),3.52(s,3H),3.38(s,3H),2.91(s,3H). 13 C NMR(100MHz,CDCl 3 )δ171.7,169.2,150.0,134.4,129.1,128.9,128.8,128.2,119.3,115.3,66.0,52.3,52.0,51.6,32.9ppm.3a': 1 H NMR(400MHz,CDCl 3 ):δ7.22-7.18(m,5H),7.12(dd,J＝8.8,7.3Hz,2H),6.70(t,J＝7.3Hz,1H),6.61(d,J＝8.2Hz,2H),5.15(d,J＝11.3Hz,1H),4.36(d,J＝11.4Hz,1H),3.71(d,J＝9.7Hz,6H),2.65(s,3H).
example 2
In this example, the amount of dichloromethane used was 4mL and the remaining steps were the same as in example 1 to give the products 3a and 3a' in a total yield of 68%. Wherein 3a (24.5 mg), 3a' (18.2 mg).
Example 3
In this example, the amount of dichloromethane used was 1mL, and the remaining steps were the same as in example 1, to give the products 3a and 3a', with a total yield of 72%. Wherein 3a (25.5 mg), 3a' (19.4 mg).
Example 4
In this example, the organic solvent was acetonitrile and the rest of the procedure was as in example 1 to give the products 3a and 3a' in 75% overall yield. Wherein 3a (23.5 mg), 3a' (18.7 mg).
Example 5
In this example the organic solvent was 1, 2-dichloroethane and the remaining procedure was as in example 1 to give the products 3a and 3a', which are diastereoisomers with a total yield of 72%. Wherein 3a (24.7 mg), 3a' (18.5 mg).
Example 6
176.2mg (1.0 mmol,5 eq) of methyl phenylacetate diazo and 35.8mg (0.2 mmol,1 eq) of methyl N-methyl-N-phenyl-glycinate were added to dichloromethane (2.0 mL) in this example, the remaining steps being identical to those of example 1, giving the products 3a and 3a', diastereoisomers with a total yield of 65%. Wherein 3a (19.2 mg), a white solid, 3a' (17.6 mg) was used as a colorless liquid.
Example 7
105.7mg (0.6 mmol,3 eq) of methyl phenylacetate diazo and 35.8mg (0.2 mmol,1 eq) of methyl N-methyl-N-phenyl-glycinate were added to dichloromethane (2.0 mL) in this example, the remaining procedure being as in example 1 to give the products 3a and 3a', diastereoisomers with a total yield of 60%. Wherein 3a (18.2 mg), a white solid, 3a' (16.8 mg) was used as the colorless liquid.
Example 8
The synthesis procedure was similar to that of example 1, except that the starting material was changed from methyl phenylacetate to methyl 4-cyanophenylacetate in 88% yield.
Synthesis of dimethyl 2- (4-cyanophenyl) -3- (methyl (phenyl) amino) succinate (3 b/3 b'): 40.3mg (0.2 mmol,1 eq) of methyl 4-cyano-phenylacetate diazo and 107.5mg (0.6 mmol,3 eq) of methyl N-methyl-N-phenylglycinate are added to dichloromethane (2 mL) at room temperature, in N 2 The reaction was irradiated for 12h under 470nm blue light. The product 3b and 3b', which are diastereoisomers with 48% overall yield, was obtained by column chromatography separation and purification (eluent V (PE): V (1, 4-dioxane) =50:1). Wherein 3b (17.9 mg) was a white solid. 3b' (15.8 mg), colorless liquid. 3b: 1 H NMR(400MHz,CDCl 3 ):δ7.64(s,4H),7.29(dd,J＝8.8,7.2Hz,2H),7.03(d,J＝7.8Hz,2H),6.88(t,J＝7.3Hz,1H),5.08(d,J＝11.6Hz,1H),4.48(d,J＝11.6Hz,1H),3.57(s,3H),3.46(s,3H),2.89(s,3H). 13 C NMR(100MHz,CDCl 3 )δ170.9,169.0,149.8,139.9,132.5,130.0,129.3,119.8,118.6,115.5,112.2,66.4,52.7,52.1,52.0,33.1ppm.3b': 1 H NMR(400MHz,CDCl 3 ):δ7.31-7.28(m,2H),7.20(d,J＝7.1Hz,1H),7.17-7.11(m,3H),6.73(t,J＝7.3Hz,1H),6.58(d,J＝8.0Hz,2H),5.16(d,J＝11.3Hz,1H),4.44(d,J＝11.3Hz,1H),3.73(d,J＝2.0Hz,6H),3.71(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ134.66,132.36,132.29,129.97,129.35,129.20,128.83,125.68,123.49,118.68,113.76,64.87,58.52,52.66,52.61,43.21ppm.
example 9
The synthesis procedure was similar to that of example 1, except that the starting material was changed from methyl phenylacetate to methyl 3-bromophenylacetate in 85% yield.
Synthesis of dimethyl 2- (3-bromobenzyl) -3- (methyl (phenyl) amino) succinate (3 c/3 c'): 51.1mg (0.2 mmol,1 eq) of methyl 3-bromo-phenylacetate diazo and 107.5mg (0.6 mmol,3 eq) of methyl N-methyl-N-phenylglycinate are added to dichloromethane (2 mL) at room temperature, in N 2 The reaction was irradiated for 12h under 470nm blue light. The product 3c and 3c', which are diastereoisomers to each other in a total yield of 47%, was obtained as a white solid, by column chromatography purification (eluent V (PE): V (1, 4-dioxane) =50:1). 3c' (15.8 mg), colorless liquid. 3c: 1 H NMR(400MHz,CDCl 3 ):δ7.67(t,J＝1.9Hz,1H),7.43(dd,J＝7.9,1.9Hz,2H),7.30(dd,J＝8.8,7.3Hz,2H),7.21(t,J＝7.9Hz,1H),7.04(d,J＝7.9Hz,2H),6.87(t,J＝7.3Hz,1H),5.06(d,J＝11.7Hz,1H),4.38(d,J＝11.7Hz,1H),3.57(s,3H),3.46(s,3H),2.90(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ171.3,169.1,149.9,136.7,132.0,131.5,130.3,129.3,127.9,122.8,119.6,115.5,66.2,52.6,52.0,51.7,33.0ppm.3c': 1 HNMR(400MHz,CDCl 3 ):δ7.41-7.33(m,3H),7.25-7.20(m,3H),7.13(t,J＝7.9Hz,1H),6.83-6.78(m,1H),6.70(d,J＝7.8Hz,2H),5.21(d,J＝11.3Hz,1H),4.41(d,J＝11.3Hz,1H),3.80(s,3H),3.78(s,3H),2.74(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ172.3,172.0,149.3,136.9,131.7,131.1,130.1,129.1,127.1,122.5,118.4,113.9,65.0,52.7,52.6,50.8,36.3ppm.
example 10
The synthesis procedure was similar to that of example 1, except that the starting material was changed from methyl phenylacetate to methyl 4-bromophenylacetate, in 87% yield.
Synthesis of dimethyl 2- (4-bromobenzyl) -3- (methyl (phenyl) amino) succinate (3 d/3 d'): 51.1mg (0.2 mmol,1 eq) of methyl 4-bromo-phenylacetate diazo and 107.5mg (0.6 mmol,3 eq) of methyl N-methyl-N-phenylglycinate are added to dichloromethane (2 mL) at room temperature, in N 2 The reaction was irradiated for 12h under 470nm blue light. The product was isolated and purified by column chromatography (eluent V (PE): V (1, 4-dioxane) =50:1) to give the product 3d and 3d', which were diastereoisomers with a total yield of 63%, product 3d (27.0 mg) as a white solid. 3d' (24.3 mg), colorless liquid. 3d: 1 H NMR(400MHz,CDCl 3 ):δ7.46(d,J＝8.2Hz,2H),7.38(d,J＝8.5Hz,2H),7.32-7.24(m,2H),7.02(d,J＝8.1Hz,2H),6.86(t,J＝7.3Hz,1H),5.04(d,J＝11.6Hz,1H),4.38(d,J＝11.7Hz,1H),3.55(s,3H),3.44(s,3H),2.89(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ171.4,169.1,149.9,133.6,132.0,130.8,129.2,122.4,119.5,115.4,66.2,52.5,51.9,51.5,33.0ppm.3d': 1 H NMR(400MHz,CDCl 3 ):δ7.33(d,J＝8.5Hz,2H),7.15(dd,J＝8.8,7.2Hz,2H),7.09(d,J＝8.5Hz,2H),6.74(t,J＝7.2Hz,1H),6.62(d,J＝7.8Hz,2H),5.12(d,J＝11.3Hz,1H),4.34(d,J＝11.3Hz,1H),3.72(s,3H),3.70(s,3H),2.65(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ172.4,172.1,149.3,133.8,131.8,130.2,129.1,122.0,118.4,113.8,64.9,52.7,52.6,50.7,34.7ppm.
example 11
The synthesis procedure was similar to that of example 1, except that the starting material was changed from methyl phenylacetate to methyl 3-chloroacetate in 85% yield.
Synthesis of dimethyl 2- (3-chlorophenyl) -3- (methyl (phenyl) amino) succinate (3 e/3 e'): 42.1mg (0.2 mmol,1 eq) of methyl 3-chloro-phenylacetate diazo and 107.5mg (0.6 mmol,3 eq) of methyl N-methyl-N-phenylglycinate are added to dichloromethane (2 mL) at room temperature, in N 2 The reaction was irradiated for 12h under 470nm blue light. The product 3e and 3e', which are diastereoisomers with a total yield of 63% and product 3e (19.0 mg) as a white solid, were obtained by column chromatography purification (eluent V (PE): V (1, 4-dioxane) =50:1). 3e' (20.3 mg), colorless liquid. 3e: 1 H NMR(400MHz,CDCl 3 ):δ7.52(s,1H),7.41-7.37(m,1H),7.33-7.23(m,4H),7.04(d,J＝8.2Hz,2H),6.87(t,J＝7.3Hz,1H),5.07(d,J＝11.6Hz,1H),4.40(d,J＝11.7Hz,1H),3.57(s,3H),3.46(s,3H),2.90(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ171.3,169.1,149.9,136.5,134.6,130.0,129.2,129.1,128.5,127.4,119.6,115.5,66.2,52.5,51.9,51.7,33.0ppm.3e': 1 H NMR(400MHz,CDCl 3 ):δ7.23(d,J＝1.8Hz,3H),7.18-7.07(m,6H),6.73(t,J＝7.3Hz,1H),6.62(d,J＝7.8Hz,2H),5.13(d,J＝11.3Hz,1H),4.34(d,J＝11.4Hz,1H),3.72(s,3H),3.71(s,3H),2.67(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ172.8,172.0,149.3,136.7,134.4,129.9,129.1,128.8,128.2,126.7,118.4,113.8,65.0,52.7,52.6,50.8,34.6ppm.
example 12
The synthesis procedure was similar to that of example 1, except that the starting material was changed from methyl phenylacetate to methyl 4-chlorophenylacetate in 85% yield.
Synthesis of dimethyl 2- (4-chlorophenyl) -3- (methyl (phenyl) amino) succinate (3 f/3 f'):42.1mg (0.2 mmol,1 eq) of methyl 4-chloro-phenylacetate diazo and 107.5mg (0.6 mmol,3 eq) of methyl N-methyl-N-phenylglycinate are added to dichloromethane (2 mL) at room temperature, in N 2 The reaction was irradiated for 12h under 470nm blue light. The product 3f and 3f', which are diastereoisomers to each other in a total yield of 63% and product 3f (23.6 mg) as a white solid, was obtained by column chromatography purification (eluent V (PE): V (1, 4-dioxane) =50:1). 3f' (21.2 mg), colorless liquid. 3f: 1 H NMR(400MHz,CDCl 3 ):δ7.44(d,J＝8.4Hz,2H),7.29(dd,J＝13.2,8.3Hz,4H),7.03(d,J＝8.1Hz,2H),6.86(t,J＝7.3Hz,1H),5.05(d,J＝11.6Hz,1H),4.39(d,J＝11.6Hz,1H),3.55(s,3H),3.44(s,3H),2.89(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ171.5,169.1,145.0,134.2,133.0,130.4,129.2,129.0,119.5,115.4,66.2,52.5,51.8,51.4,33.0ppm.3f'： 1 H NMR(400MHz,CDCl 3 ):δ7.09(d,J＝2.7Hz,4H),7.08-7.04(m,2H),6.65(t,J＝7.3Hz,1H),6.57-6.50(m,2H),5.04(d,J＝11.3Hz,1H),4.28(d,J＝11.4Hz,1H),3.63(d,J＝8.2Hz,7H),2.58(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ172.5,172.1,149.3,133.9,133.3,129.8,129.1,128.8,118.4,113.8,64.9,52.7,52.5,50.6,34.7ppm.
example 13
The synthesis procedure was similar to that of example 1, except that the starting material was changed from methyl phenylacetate to methyl 3-trifluoromethylphenylacetate, with a yield of 88%.
Synthesis of dimethyl 2- (methyl (phenyl) amino) -3- (3- (trifluoromethyl) phenyl) succinate (3 g/3 g'): 1 h NMR (400 MHz,7.78-7.71 (m, 2H), 7.57 (d, J=7.8 Hz, 1H), 7.47 (t, J=room temperature), 48.8mg (0.2 mmol,1 eq) of methyl 3-trifluoromethyl-phenylacetate diazonium and 107.5mg (0.6 mmol,3 eq) of methyl N-methyl-N-phenylglycinate were added to dichloromethane (2 mL) at N 2 The reaction was irradiated for 12h under 470nm blue light. The product was isolated and purified by column chromatography (eluent V (PE): V (1, 4-dioxane) =50:1) to give 3g and 3g' of the product as diastereoisomers, 46% overall yield, 3g (16.7 mg) of the product as a white solid. 3g' (19.5 mg) of a colorless liquid. 3g: 1 H NMR(400MHz,CDCl 3 ):δ7.78-7.71(m,2H),7.57(d,J＝7.8Hz,1H),7.47(t,J＝7.8Hz,1H),7.33-7.27(m,2H),7.05(d,J＝7.9Hz,2H),6.88(t,J＝7.3Hz,1H),5.09(d,J＝11.6Hz,1H),4.49(d,J＝11.6Hz,1H),3.58(s,3H),3.44(s,3H),2.92(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ171.3,169.1,149.9,135.6,132.5,129.3,129.3,126.0,125.9,125.2,125.2,119.7,115.6CDCl 3 ):δ,66.4,52.6,51.9,51.8,33.1ppm.3g'： 1 H NMR(400MHz,CDCl 3 ):δ7.42(dd,J＝17.1,8.1Hz,3H),7.30(t,J＝7.6Hz,3H),7.12(dd,J＝8.9,7.3Hz,2H),5.18(d,J＝11.3Hz,1H),4.44(d,J＝11.3Hz,1H),3.74(s,3H),3.72(s,3H),2.65(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ172.2,172.0,150.9,149.2,135.8,131.9,129.2,129.1,129.0,128.7,123.5,118.5,113.8,65.0,58.6,51.0,43.1,34.6ppm.
example 14
The synthesis procedure was similar to that of example 1, except that the starting material was changed from methyl phenylacetate to methyl 4-benzyloxyphenylacetate, with a yield of 82%.
Synthesis of dimethyl 2- (4- (benzoyloxy) phenyl) -3- (methyl (phenyl) amino) succinate (3 h/3 h'): 56.5mg (0.2 mmol,1 eq) of methyl 4-benzyloxy-phenylacetate diazo and 107.5mg (0.6 mmol,3 eq) of methyl N-methyl-N-phenylglycinate are added to dichloromethane (2 mL) at room temperature, in N 2 The reaction was irradiated for 12h under 470nm blue light. Separating and purifying by column chromatography (eluent is V (PE): V (1, 4-dioxane) =50:1) to obtain products 3h and 3h', which are diastereoisomersThe total yield was 48%, product 3h (23.8 mg), white solid; 3h' (17.8 mg), colorless liquid. 3h: 1 H NMR(400MHz,CDCl 3 ):δ7.47-7.38(m,6H),7.35(d,J＝7.0Hz,1H),7.31(dd,J＝8.8,7.2Hz,2H),7.06(d,J＝7.8Hz,2H),6.97(d,J＝8.7Hz,2H),6.87(t,J＝7.3Hz,1H),5.09(d,J＝11.7Hz,1H),5.06(s,2H),4.39(d,J＝11.7Hz,1H),3.57(s,3H),3.44(s,3H),2.94(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ172.0,169.3,158.7,150.0,136.9,130.1,129.2,128.7,128.1,127.6,126.6,119.2,115.3,115.1,70.1,66.1,52.3,51.7,51.2,32.9ppm.3h'： 1 H NMR(400MHz,CDCl 3 ):δ7.38(d,J＝5.3Hz,4H),7.36-7.32(m,1H),7.14(d,J＝8.7Hz,4H),6.81(d,J＝8.7Hz,2H),6.72(t,J＝7.3Hz,1H),6.64(d,J＝7.6Hz,2H),5.11(d,J＝11.3Hz,1H),4.97(s,2H),4.32(d,J＝11.3Hz,1H),3.71(d,J＝8.5Hz,6H),2.66(s,3H).
example 15
The synthesis procedure was similar to that of example 1, except that the starting material was changed from methyl phenylacetate to methyl 4-methoxyphenylacetate, with a yield of 90%.
Synthesis of dimethyl 2- (4-methoxyphenyl) -3- (methyl (phenyl) amino) succinate (3 i/3 i'): 41.2mg (0.2 mmol,1 eq) of methyl 4-methoxy-phenylacetate diazo and 107.5mg (0.6 mmol,3 eq) of methyl N-methyl-N-phenylglycinate are added to dichloromethane (2 mL) at room temperature, in N 2 The reaction was irradiated for 12h under 470nm blue light. Separating and purifying by column chromatography (eluent V (PE): V (1, 4-dioxane) =50:1) to give products 3i and 3i', which are diastereoisomers with 60% overall yield, product 3i (22.9 mg) as a white solid; 3i' (22.5 mg), colorless liquid. 3i: 1 H NMR(400MHz,CDCl 3 ):δ7.40(d,J＝8.7Hz,2H),7.31-7.21(m,2H),7.02(d,J＝7.7Hz,2H),6.83(dd,J＝11.1,8.0Hz,3H),5.05(d,J＝11.7Hz,1H),4.35(d,J＝11.7Hz,1H),3.76(s,3H),3.53(s,3H),3.41(s,3H),2.90(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ172.0,169.3,159.5,150.0,130.1,129.2,126.4,119.2,115.3,114.2,66.1,55.3,52.3,51.7,51.1,32.9ppm.3i'： 1 H NMR(400MHz,CDCl 3 ):δ7.17-7.05(m,5H),6.71(dd,J＝11.0,8.0Hz,3H),6.62(d,J＝7.7Hz,2H),5.10(d,J＝11.3Hz,1H),4.30(d,J＝11.3Hz,1H),3.69(d,J＝9.0Hz,9H),2.65(s,3H). 13 C NMR(101MHz,CDCl 3 ):δ173.1,172.3,159.2,149.5,129.5,129.0,126.7,118.0,114.0,113.7,65.0,55.3,52.5,52.4,50.3,34.5ppm.
example 16
The synthesis procedure was similar to that of example 1, except that the starting material was changed from methyl phenylacetate to methyl 4-fluorophenylacetate, with a yield of 86%.
Synthesis of dimethyl 2- (4-fluorophenyl) -3- (methyl (phenyl) amino) succinate (3 j/3 j'): 38.8mg (0.2 mmol,1 eq) of methyl 4-fluoro-phenylacetate diazo and 107.5mg (0.6 mmol,3 eq) of methyl N-methyl-N-phenylglycinate are added to dichloromethane (2 mL) at room temperature, in N 2 The reaction was irradiated for 12h under 470nm blue light. Separating and purifying by column chromatography (eluent V (PE): V (1, 4-dioxane) =50:1) to obtain products 3j and 3j', which are diastereoisomers with a total yield of 72%, product 3j (24.3 mg) as a white solid; 3j' (25.4 mg), colorless liquid. 3j: 1 H NMR(400MHz,CDCl 3 ):δ7.48(dd,J＝8.6,5.4Hz,2H),7.31-7.24(m,2H),7.07-6.99(m,4H),6.85(t,J＝7.2Hz,1H),5.05(d,J＝11.6Hz,1H),4.40(d,J＝11.7Hz,1H),3.55(s,3H),3.42(s,3H),2.91(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ171.7,169.2,163.9,161.4,150.0,130.8,130.7,130.3,130.2,129.2,119.4,115.8,115.6,115.4,66.3,52.4,51.7,51.2,32.9ppm.3j'： 1 H NMR(400MHz,CDCl 3 ):δ7.16(ddd,J＝18.8,8.7,6.3Hz,4H),6.89(t,J＝8.7Hz,2H),6.72(t,J＝7.2Hz,1H),6.61(d,J＝7.8Hz,2H),5.12(d,J＝11.3Hz,1H),4.36(d,J＝11.3Hz,1H),3.72(s,3H),3.70(s,3H),2.66(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ172.7,172.1,163.6,161.2,149.3,130.5,130.5,130.1,130.1,129.1,118.3,115.7,115.5,113.7,65.0,52.6,52.5,50.4,34.6ppm.
example 17
The synthesis procedure was similar to that of example 1, except that the starting material was changed from methyl phenylacetate to methyl 4-tert-butylphenylacetate, with a yield of 88%.
Synthesis of dimethyl 2- (4- (tert-butyl) phenyl) -3- (methyl (phenyl) amino) succinate (3 k/3 k'): 46.5mg (0.2 mmol,1 eq) of methyl 4-tert-butyl-phenylacetate diazo and 107.5mg (0.6 mmol,3 eq) of methyl N-methyl-N-phenylglycinate are added to dichloromethane (2 mL) at room temperature, in N 2 The reaction was irradiated for 12h under 470nm blue light. The product 3k and 3k', which are diastereoisomers to each other in a total yield of 55% and the product 3k (25.7 mg) as a white solid, was obtained by column chromatography purification (eluent V (PE): V (1, 4-dioxane) =50:1). 3k' (22.8 mg), colorless liquid. 3k: 1 HNMR(400MHz,CDCl 3 ):δ7.40(d,J＝8.5Hz,2H),7.32(d,J＝8.4Hz,2H),7.29-7.22(m,2H),7.02(d,J＝7.9Hz,2H),6.82(t,J＝7.3Hz,1H),5.08(d,J＝11.7Hz,1H),4.39(d,J＝11.7Hz,1H),3.52(s,3H),3.39(s,3H),2.90(s,3H),1.28(s,9H). 13 C NMR(100MHz,CDCl 3 ):δ171.9,169.4,151.1,150.1,131.3,129.2,128.6,125.7,119.2,115.3,66.0,52.3,51.7,51.6,34.6,32.9,31.4ppm.3k'： 1 H NMR(400MHz,CDCl 3 ):δ7.19(d,J＝8.4Hz,2H),7.16-7.08(m,4H),6.73-6.66(m,1H),6.60(d,J＝7.8Hz,2H),5.13(d,J＝11.3Hz,1H),4.34(d,J＝11.3Hz,1H),3.72(s,3H),3.70(s,3H),2.66(s,3H),1.23(s,9H). 13 C NMR(100MHz,CDCl 3 ):δ173.0,172.3,150.8,149.7,131.5,128.9,128.1,125.5,118.1,114.1,65.4,52.5,52.4,50.6,34.5,34.4,31.3ppm.
example 18
Synthesis of methyl-N-m-tolylglycine methyl ester: in a 100mL reaction flask, N-methyl-N-m-toluidine (1.1 mL,10 mmol) and methyl bromoacetate (1.1 mL,12 mmol) were dissolved in 15mL of methanol, and anhydrous potassium carbonate (530 mg,5 mmol) was added thereto and the mixture was refluxed for 4 hours. Then, the potassium carbonate is removed by suction filtration, the solvent is removed under reduced pressure, and the product N-methyl-N-m-tolylglycine methyl ester is obtained with a yield of 86% by separation and purification by column chromatography (eluent is V (PE): V (EA) =20:1).
Synthesis of dimethyl 2- (m-tolyl) amino) -3-phenylsuccinate (3 l/3 l'): 35.2mg (0.2 mmol,1 eq) of methyl phenylacetate diazo and 116.0mg (0.6 mmol,3 eq) of methyl N-methyl-N-m-tolylglycine are added to dichloromethane (2 mL) at room temperature, in N 2 The reaction was irradiated for 12h under 470nm blue light. Separating and purifying by column chromatography (eluent V (PE): V (1, 4-dioxane) =50:1) to obtain product 3l and 3l', which are diastereoisomers with each other, total yield 69%, product 3l (25.3 mg), white solid; 3l' (21.7 mg) of a colorless liquid. 3l: 1 H NMR(400MHz,CDCl 3 ):δ7.51(d,J＝7.2Hz,2H),7.33(dt,J＝12.9,7.3Hz,3H),7.18(t,J＝7.7Hz,1H),6.91-6.83(m,2H),6.69(d,J＝7.2Hz,1H),5.12(d,J＝11.6Hz,1H),4.42(d,J＝11.7Hz,1H),3.57(s,3H),3.42(s,3H),2.93(s,3H),2.36(s,3H). 13 C NMR(100MHz,CDCl 3 ):δ171.8,169.4,150.1,138.9,134.5,129.1,129.0,128.8,128.2,120.3,116.1,112.6,66.0,52.3,52.1,51.7,33.0,22.0ppm.3l': 1 H NMR(400MHz,CDCl 3 ):δ7.25-7.17(m,5H),7.01(t,J＝7.8Hz,1H),6.52(d,J＝7.4Hz,1H),6.42(dd,J＝11.9,3.8Hz,2H),5.14(d,J＝11.4Hz,1H),4.35(d,J＝11.3Hz,1H),3.71(d,J＝7.4Hz,6H),2.64(s,3H),2.23(s,3H).
example 19
The synthesis procedure was similar to that of N-methyl-N-m-tolylglycine methyl ester in example 18, except that N-methyl-N-m-toluidine was changed to N-methylaniline, methyl bromoacetate was changed to ethyl bromoacetate, and the yield was 70%.
Synthesis of 1-methyl 4-methyl 2- (methyl (phenyl) amino) -3-phenylsuccinate (3 m/3 m'): 35.2mg (0.2 mmol,1 eq) of methyl phenylacetate diazo and 116.0mg (0.6 mmol,3 eq) of ethyl N-methyl-N-m-tolylglycine are added to dichloromethane (2 mL) at room temperature, at N 2 The reaction was irradiated for 12h under 470nm blue light. Separating and purifying by column chromatography (eluent V (PE): V (1, 4-dioxane) =50:1) to obtain products 3m and 3m', which are diastereoisomers with a total yield of 70%, product 3m (27.2 mg) as a white solid; 3m' (20.9 mg), colorless liquid. 3m: 1 H NMR(400MHz,CDCl 3 ):δ7.49(s,2H),7.36-7.24(m,5H),7.05(d,J＝7.7Hz,2H),6.84(t,J＝7.2Hz,1H),5.09(d,J＝11.7Hz,1H),4.40(d,J＝11.7Hz,1H),3.93-3.81(m,2H),3.55(s,3H),2.95(s,3H),0.90(t,J＝7.1Hz,3H). 13 C NMR(100MHz,CDCl 3 ):δ171.9,168.8,150.2,134.5,129.1,128.8,128.2,119.3,115.5,66.2,60.7,52.3,52.1,33.0,14.1ppm.3m'： 1 H NMR(400MHz,CDCl 3 ):δ7.25-7.17(m,5H),7.15-7.09(m,2H),6.73-6.67(m,1H),6.62(d,J＝7.8Hz,2H),5.12(d,J＝11.4Hz,1H),4.36(d,J＝11.3Hz,1H),4.19(dddd,J＝17.9,10.8,7.1,3.6Hz,2H),3.70(s,3H),2.66(s,3H),1.20(t,J＝7.1Hz,3H).
example 20
The synthesis procedure was similar to that of N-methyl-N-m-tolylglycine methyl ester in example 18, except that the raw material N-methyl-N-m-toluidine was changed to N-methyl-N-p-trifluoromethylaniline, and the yield was 56%.
Synthesis of dimethyl 2- (methyl (4- (trifluoromethyl) phenyl) amino) -3-phenylsuccinate (3 n/3 n'): 35.2mg (0.2 mmol,1 eq) of methyl phenylacetate diazo and 148.3mg (0.6 mmol,3 eq) of methyl N-methyl-N-p-trifluoromethylglycine are added to dichloromethane (2 mL) at room temperature, at N 2 The reaction was irradiated for 12h under 470nm blue light. Separating and purifying by column chromatography (eluent V (PE): V (1, 4-dioxane) =50:1) to obtain products 3n and 3n', which are diastereoisomers with a total yield of 70%, product 3n (18.9 mg) as a white solid; 3n' (16.4 mg), colorless liquid. 3n: 1 H NMR(400MHz,CDCl 3 ):δ7.50(dd,J＝11.2,7.9Hz,4H),7.39-7.29(m,3H),7.05(d,J＝8.6Hz,2H),5.17(d,J＝11.6Hz,1H),4.42(d,J＝11.5Hz,1H),3.55(s,3H),3.45(s,3H),2.99(s,3H).3n'： 1 H NMR(400MHz,CDCl 3 ):δ7.28(d,J＝8.7Hz,2H),7.12(s,5H),6.56(d,J＝8.6Hz,2H),5.15(d,J＝11.3Hz,1H),4.29(d,J＝11.3Hz,1H),3.67(s,3H),3.64(s,3H),2.62(s,3H).
example 21
The synthesis procedure was similar to that of N-methyl-N-m-tolylglycine methyl ester in example 18, except that the raw material N-methyl-N-m-toluidine was changed to N-methyl-N-p-methylaniline, and the yield was 80%.
Synthesis of dimethyl 2- (methyl (p-tolyl) amino) -3-phenylsuccinate (3 o/3 o'): 35.2mg (0.2 mmol,1 eq) of methyl phenylacetate are reacted at room temperatureDiazo and 115.9mg (0.6 mmol,3 eq) of N-methyl-N-p-tolylglycine methyl ester are added to methylene chloride (2 mL), in N 2 The reaction was irradiated for 12h under 470nm blue light. Separating and purifying by column chromatography (eluent V (PE): V (1, 4-dioxane) =50:1) to obtain products 3o and 3o', which are diastereoisomers with a total yield of 68%, product 3o (21.9 mg) as a white solid; 3o' (19.8 mg), colorless liquid, yield 68%.3o: 1 H NMR(400MHz,CDCl 3 ):δ7.52-7.48(m,2H),7.37-7.28(m,3H),7.09(d,J＝7.9Hz,2H),6.97(d,J＝8.6Hz,2H),5.05(d,J＝11.7Hz,1H),4.40(d,J＝11.7Hz,1H),3.58(s,3H),3.41(s,3H),2.89(s,3H),2.28(s,3H).3o': 1 H NMR(400MHz,CDCl 3 ):δ7.25-7.18(m,5H),6.93(d,J＝8.4Hz,2H),6.52(d,J＝8.6Hz,2H),5.07(d,J＝11.4Hz,1H),4.34(d,J＝11.4Hz,1H),3.70(d,J＝4.8Hz,6H),2.63(s,3H),2.20(s,3H).
example 22
Synthesis of N-methyl-N-phenylglycine cyclohexyl ester: in a 100mL clean reaction flask, N-methylaniline (1.1 mL,10 mmol) and cyclohexyl vinyl ether (2.8 mL,20 mmol) were dissolved in 20mL DMF, and palladium acetate (112 mg,0.5 mmol) and 30% hydrogen peroxide solution (4 mL,40 mmol) were added and reacted at 70℃for 12h. After completion the mixture was diluted with water, saturated NH 4 The mixture was neutralized with Cl, extracted three times with ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and purified by column chromatography (eluent V (PE): V (EA) =150:1) to give the product N-methyl-N-phenylglycine cyclohexyl ester in 50% yield.
Synthesis of cyclohexyl 4-methyl 2- (methyl (phenyl) amino) -3-phenylsuccinate (3 p/3 p'): 35.2mg (0.2 mmol,1 eq) of methyl phenylacetate diazo and 148.3mg (0.6 mmol,3 eq) of N-methyl-N-m-tolylglycine cyclohexyl are added to dichloromethane (2 mL) at room temperature, in N 2 The reaction was irradiated for 12h under 470nm blue light. The product 3p and 3p', which are diastereoisomers to each other in 39% overall yield, product 3p (17.8 mg) as a white solid, was obtained by column chromatography purification (eluent V (PE): V (1, 4-dioxane) =50:1). 3p' (13.2 mg), colorless liquid. 3p: 1 H NMR(400MHz,CDCl 3 ):δ7.50(d,J＝6.5Hz,2H),7.36-7.24(m,6H),7.05(d,J＝8.2Hz,2H),6.84(t,J＝7.3Hz,1H),5.08(d,J＝11.8Hz,1H),4.53(tt,J＝8.0,3.6Hz,1H),4.40(d,J＝11.8Hz,1H),3.57(s,3H),2.96(s,3H),1.63-1.33(m,6H),1.26(s,2H),1.17(q,J＝10.3Hz,5H),1.03(t,J＝9.5Hz,1H),0.89(d,J＝6.2Hz,1H). 13 C NMR(100MHz,CDCl 3 ):δ171.9,168.2,150.3,134.6,129.1,129.1,128.7,128.2,119.2,115.6,73.1,66.7,52.3,52.1,33.0,31.3,31.2,23.4ppm.3p'： 1 H NMR(400MHz,CDCl 3 ):δ7.26-7.18(m,5H),7.15-7.09(m,2H),6.69(t,J＝7.3Hz,1H),6.63(d,J＝7.9Hz,2H),5.10(d,J＝11.4Hz,1H),4.84(tt,J＝8.4,3.9Hz,1H),4.35(d,J＝11.4Hz,1H),3.69(s,3H),2.66(s,3H),1.77(s,1H),1.69(s,1H),1.61(s,1H),1.54(s,1H),1.44(d,J＝9.4Hz,2H),1.39-1.16(m,6H).
example 23
The synthesis procedure was similar to that of N-methyl-N-m-tolylglycine methyl ester in example 18, except that the raw material N-methyl-N-m-toluidine was changed to N-methyl-N-m-chloroaniline, and the yield was 65%.
Synthesis of dimethyl 2- ((3-chlorophenyl) (methyl) amino) -3-phenylsulfate (3 q/3 q'): 35.2mg (0.2 mmol,1 eq) of methyl phenylacetate diazo and 128.2mg (0.6 mmol,3 eq) of methyl N-methyl-N-m-chlorophenyl glycine are added to dichloromethane (2 mL) at room temperature, at N 2 The reaction was irradiated for 12h under 470nm blue light. Separating and purifying by column chromatography (eluent is V (PE): V (1, 4-dioxane) =50:1) to obtain products 3q and 3q', which are diastereoisomericThe complete yield was 46%, product 3q (15.7 mg), white solid. 3q' (12.5 mg), colorless liquid. 3q: 1 H NMR(400MHz,CDCl 3 ):δ7.27(d,J＝6.7Hz,2H),7.11(dd,J＝11.6,7.1Hz,3H),6.98(t,J＝8.0Hz,1H),6.73(d,J＝8.0Hz,2H),6.60(d,J＝6.3Hz,1H),4.85(d,J＝11.6Hz,1H),4.18(d,J＝11.6Hz,1H),3.35(s,3H),3.22(s,3H),2.70(s,3H).3q'： 1 H NMR(400MHz,CDCl 3 ):δ7.21(s,5H),7.02(t,J＝8.1Hz,1H),6.65(d,J＝6.7Hz,1H),6.55-6.47(m,2H),5.13(d,J＝11.3Hz,1H),4.33(d,J＝11.3Hz,1H),3.74(s,3H),3.70(s,3H),2.64(s,3H).
example 24
The synthesis procedure was similar to that of N-methyl-N-m-tolylglycine methyl ester in example 18, except that the raw material N-methyl-N-m-toluidine was changed to N-methyl-N-p-chloroaniline, and the yield was 80%.
Synthesis of dimethyl 2- ((4-chlorophenyl) (methyl) amino) -3-phenylsulfate (3 r/3 r'): 35.2mg (0.2 mmol,1 eq) of methyl phenylacetate diazo and 128.2mg (0.6 mmol,3 eq) of methyl N-methyl-N-p-chlorophenyl glycine are added to dichloromethane (2 mL) at room temperature, at N 2 The reaction was irradiated for 12h under 470nm blue light. Separating and purifying by column chromatography (eluent V (PE): V (1, 4-dioxane) =50:1) to obtain products 3r and 3r', which are diastereoisomers with a total yield of 70%, product 3r (22.7 mg) as a white solid; 3r' (19.3 mg), colorless liquid. 3r: 1 H NMR(400MHz,CDCl 3 ):δ7.48(d,J＝6.5Hz,2H),7.37-7.29(m,3H),7.22(d,J＝9.0Hz,2H),6.96(d,J＝9.0Hz,2H),5.02(d,J＝11.7Hz,1H),4.39(d,J＝11.7Hz,1H),3.57(s,3H),3.42(s,3H),2.90(s,3H).3r'： 1 H NMR(400MHz,CDCl 3 ):δ7.26(s,5H),7.11(d,J＝9.0Hz,2H),6.57(d,J＝9.0Hz,2H),5.14(d,J＝11.3Hz,1H),4.39(d,J＝11.3Hz,1H),3.79(s,3H),3.75(s,3H),2.69(s,3H)。
Claims (5)
1. a method for synthesizing a butanedicarboxylate derivative by visible light catalysis is characterized in that reaction raw materials of amino acetate and aryl diazoacetate are dissolved in an organic solvent, then a reaction system is placed in a nitrogen atmosphere, stirred at room temperature for reaction under blue light, and separated and purified to obtain the butanedicarboxylate derivative, wherein the structural formula of the butanedicarboxylate derivative is shown as a formula (1):
，
wherein R is 1 、R 2 Each independently is any one of alkyl, alkoxy, aryl; or R is 1 、R 2 Is a constituent part of the same annular structure;
R 3 、R 4 and R is 5 Each independently is any one of alkyl, aryl, allyl.
2. The method for synthesizing the butanedicarboxylate derivative by using visible light as defined in claim 1, wherein the molar ratio of the amino acetate to the aryl diazoacetate serving as the reaction raw materials is 2-30:6.
3. The method for synthesizing the butanedicarboxylate derivative by using visible light as claimed in claim 1, wherein the molar concentration of the reaction raw material in the organic solvent is 0.05-0.8 mol/L.
4. The method for synthesizing a butanedicarboxylate derivative by visible light catalysis according to claim 1, wherein the organic solvent is dichloromethane, 1, 2-dichloroethane, or chloroform.
5. The method for synthesizing the butanedicarboxylate derivative by using the visible light catalysis according to claim 1, wherein the wavelength of the blue light is 450-500 nanometers.
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